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Antitumor action of rhodium (I) and iridium (I) complexes.

Several rhodium(I) and iridium(I) complexes displayed different degrees of antitumour activity when tested in mice bearing Ehrlich ascites carcinoma. Rhodium (I) and iridium (I) acetylacetonate derivatives caused a high percentage of cures. The rhodium (I) dimers were particularly interesting, since (bis(cycloocta-1,5-diene)micromicron' dichlorodirhodium(I) [RhCODCl]2) was highly effective, whereas its analogues, bis(bicyclo[2,2,1]hepta-2,5-diene)micromicron'-dichlorodirhodium(I) [RhNBDCl]2) and bis(1,5-hexadiene)micromicron' dichlorodirhodium(I) [RhEDCl]2) were virtually inactive. The absence of significant inhibition of DNA, RNA and protein syntheses in tumour cells found for [RhCODCl]2 at therapeutically active dosages, indicates that this substance has a different mechanism of action from that of cis-dichlorodiammine Pt(II) (cis-PDD). The amount of rhodium found in tumour cells after administration of active [RhCODCl]2 was higher than that for [RhEDCl]2, while the rhodium concentration in the ascitic fluid was much higher for [RhEDCl]2. A mechanism based on the chemical properties of the complexes is tentatively proposed for explaining these findings and selective toxicity for tumour cells.

Animals

[A projector of iridium 192 wires: motivations and preliminary studies (author's transl)].

Though the majority of procedures involved in curietherapy with Iridium 192 wires cause very few problems concerning radiation protection, this is not true in all cases: in elderly of debilitated patients, young children, or when using special techniques (curietherapy for prostate of bladder cancers for example). In these cases, the need for frequent treatments exposes the therapists to increased doses. The projector of Iridium 192 wires was conceived in order to reduce this irradiation hazard. A simple manipulation places the radioactive wires in a lead container during treatment, and then replaces them in the right position after therapy. This apparatus appears to offer the possibility of: an almost total protection of the therapists, and thus an opportunity for enlarging the indications for curietherapy; an improved quality of treatment to the patient during the application.

Aged

Combination teletherapy and iridium implantation in the treatment of locally advanced breast cancer.

Combined teletherapy and interstitial iridium 192 implantation can control locally advanced breast cancer in a consistent fashion without causing significant morbidity. Moreover, in the absence of clinically evident distant metastases, patients who undergo this treatment can survive comfortably for long periods of time. Among 11 patients followed for at least 1 1/2 years, nine are alive without evidence of disease, one is living with distant metastases, and one patient is dead. There has been no local recurrence in the 18 patients included in this report.

Adult

Post-operative stereotactic Curie-therapy using the iridium-192 GammaMed contact irradiation apparatus combined with radio-sensitizers in treating multiform glioblastomas.

Experimental investigations on the dimethyl-amino-stilbous carcino-sarcoma of the rat have led to a modified interstitial post-operative Curie-therapy of gliomas in the brain hemispheres following treatment with radio sensitizers. After treatment with the thymine-analogous radio-sensitizers 5-brom-2-desoxyuridine (BUDR) and 5-brom-2-desoxycytidine (BCDR) and desoxyguanosine as well as the anti-metabolites 5-fluor-uracile (FU) and methotrexate (Mtx), there is greater incorporation of the thymine analogues in the DNS of the tumour cells. More than any other combination, BUDR and Mtx effectively sensibilizes the tumour cells. Syncavit and actinomycine-D are also effective. After radio-sensitizing the post-iridium-192 contact irradiation apparatus on 133 patients with gliomas. This treatment lengthened postoperative survival times.

Brain Neoplasms

Use of an iridium electrode for direct measurements of pI of proteins after isoelectric focusing in polyacrylamide gel.

The use of an iridium microelectrode 0.5 mm in diameter is proposed for measuring the pH gradient in polyacrylamide gels after isoelectric focusing. The electrode exhibits a perfectly linear potential/pH relationship; thus it can be used directly in conjunction with a pH meter using the pH scale for readings. pH equilibrium values are rapidly reached (10-15 s) and pI determinations are obtainable with good accuracy (better than 0.1 pH).

Calorimetry

A modified afterloading technique for small implants using iridium-192 wires for interstitial therapy.

A new method is described for small iridium-192 wire implants upon the skin of the face. The method is a miniaturisation of a technique described previously (Paine, 1972), and has the advantage that is results in less scarring and therefore a better cosmetic end-result than in the case when the more conventional wide-bore tubing is employed. This new method produces similar clinical results in terms of tumour cure to other methods, and a degree of after-loading helps in radiation protection.

Carcinoma, Squamous Cell

After-loading transperineal iridium-192 wire implantation of the prostate.

Aided by suprapubic surgical access, after-loading transperineal iridium-192 wire implantations have been done for prostatic cancer in 16 patients, with major complications in 3. Personnel exposure is reduced, and, more especially, precision and flexibility of dose control and source geometry are improved. The technique is thought to render permanent implantation with grains or seeds obsolete.

Humans

An iridium-192 mold for use in treating carcinoma of the soft palate.

A Lucite sandwich mold containing Iridium-192 wire for use in the treatment of soft palate carcinoma is described. This mold is very simple to use, produces a homogeneous (+/- 10%) radiation field across the midplane of the tumor, and requires minimal machinist time.

Brachytherapy

Production of weanling rat ventromedial and dorsomedial hypothalamic syndromes by electrolytic lesions with platinum-iridium electrodes.

Weanling Sprague-Dawley rats received bilateral anodic electrolytic lesions with platinum-iridium (PtIr) electrodes in the ventromedial (VMN) and dorsomedial (DMN) hypothalamic areas. Sham-operated rats served as controls. The rats were maintained for 48 days (experiment 1) and 33 days (experiment 2) and food intake, body weight (b.w.), nose-tail length and obesity index were recorded. The data of both experiments indicate that all parameters change in the same direction, as they do when lesions are produced with anodic stainless steel electrodes: in the VMN-P-lesioned animals, b.w. gains and overall mean food intake were normal, carcass fat increased and linear growth was reduced. In experiment 2, however, there was a temporary hyperphagia during the 1st 2 weeks of the study. In the DMN-lesioned rats, both ponderal and linear growth and food intake were decreased but body composition was normal. Plasma obtained at sacrifice in experiment 2 showed slight but significant hyperinsulinemia in the VMN rats (p less than 0.02 vs control and p less than 0.05 vs DMN rats). Prolactin (PRL) levels, on the other hand, were higher in the DMN-lesioned rats (p less than 0.05 vs control and p less than 0.02 vs VMN rats). The data indicate that the changes characteristic of the weanling rat VMN and DMN syndrmes are due to 'true' tissue destruction rather than to artifactitious side effects of the lesions. They also suggest, therefore, than an 'irritative focus' hypothesis is not required to account for the observed alterations. They further suggest that the DMN may play role in the control of PRL release.

Animals

Angiocardiography with iridium-191m: an ultrashort-lived radionuclide (T1/2 4.9 sec).

Iridium-191m is a potential tracer for angiocardiography and may be of particular value in the evaluation of heart disease in children. It possesses a short half-life (4.9 sec), suitable photon energy (129 keV) and may be obtained as a generator product by decay of its long lived (15.3 day) parent 191 Os. An 191Os leads to 191mIr generator capable of providing 15 mCi of 191mIr in 1.5 ml of eluant is described. The separation of 191mIr from 191Os is achieved by absorbing 191OsC16-2 on an anion exchange resin. The generator employs an additional resin column which is replaced to prevent 191Os breakthrough to become excessive. By this procedure, the breakthrough may be kept below 0.001% over a period of at least one month and after multiple elutions.

Angiocardiography

Treatment of penis carcinoma with interstitially administered iridium; comparison with radium therapy.

The results of treatment of 30 patients with penis carcinoma cured with radium and 18 patients treated with 192Ir were compared. In both groups of patients, core assessed at 3 years was obtained for a similar percentage of patients (89% and 83%). After treatment with 192Ir, radiation necrosis was observed in 16%, and after treatment with radium in 50% of patients. In both groups a similar high percentage of patients (88%) with organs preserved after treatment was found. In group of patients treated with 192Ir the percentage of very good functional effects (69%) was much higher in the group of patients treated with radium (28%).

Adult

Five years' experience with the gold button technique for intraoral interstitial implants with iridium-192 seeds.

To simulate crossing of the ends in standard removable interstitial implants, we used the loop technique for intraoral tumors when treating them with afterloading interstitial removable implants. Because of technical problems, we changed to a straight tube method with heavy end-loading to compensate for the uncrossed ends. High doses to the normal mucosa close to heavy end-loading is reduced 2.5 times by the use of gold buttons in place of standard stainless steel buttons, thus decreasing unnecessary mucosal reactions and morbidity.

Dental Implantation

[Iridium 192 interstitial radiotherapy of carcinoma of the penis. Carcinologic results, dermatologic evaluation (about 87 cases) (author's transl)].

87 cases of epidermoid carcinoma of the penis treated by Ir 192 interstitial radiotherapy are studied. The 5 years survival rate, estimated on a 51 patients group, is 61 p. 100. Among these 51 patients, 12 had a local recurrence. The post-radiotherapy early reaction is estimated on a 79 patients group, with a mean duration of 3, 4 months. The early reaction is correlated to tumor size and not correlated to number of radio-active lines. The later dermatologic evolution is studied in 59 patients. In 22 cases, the scar remained supple, without any further local change. Local changes occurring in the 37 other cases are studied in their clinical aspect, signification and frequency. Of 34 patients followed longer than 40 months, 14 had local complications with 4 cases of local recurrence. The carcinologic reliability of this method is similar to that by surgery. It seems however it must be restricted to tumors limited to glans penis.

Adult